Potential roles of microRNA‐29a in the molecular pathophysiology of T‐cell acute lymphoblastic leukemia. Issue 10 (21st September 2015)

• Record Type: Journal Article
• Authors: Oliveira, Lucila H.; Schiavinato, Josiane L.; Fráguas, Mariane S.; Lucena‐Araujo, Antonio R.; Haddad, Rodrigo; Araújo, Amélia G.; Dalmazzo, Leandro F.; Rego, Eduardo M.; Covas, Dimas T.; Zago, Marco A.; Panepucci, Rodrigo A.
• Is Part Of: Cancer science. Volume 106:Issue 10(2015:Oct.)
• Page Start: 1264
• Page End: 1277
• Publication Date: 2015-09-21
• Subjects: DNMT -- epigenetic regulation -- miR‐29a -- T‐cell acute lymphoblastic leukemia -- TET; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.12766
• Languages: English
• ISSNs: 1347-9032

Abstract

Abstract : Recent evidence has shown that deregulated expression of members of the microRNA‐29 (miR‐29) family may play a critical role in human cancer, including hematological malignancies. However, the roles of miR‐29 in the molecular pathophysiology of T‐cell acute lymphoblastic leukemia (T‐ALL) has not been investigated. Here, we show that lower levels of miR‐29a were significantly associated with higher blast counts in the bone marrow and with increased disease‐free survival in T‐ALL patients. Furthermore, miR‐29a levels are extremely reduced in T‐ALL cells compared to normal T cells. Microarray analysis following introduction of synthetic miR‐29a mimics into Jurkat cells revealed the downregulation of several predicted targets (CDK6, PXDN, MCL1, PIK3R1, and CXXC6), including targets with roles in active and passive DNA demethylation (such as DNMT3a, DNMT3b, and members of the TET family and TDG). Restoring miR‐29a levels in Jurkat and Molt‐4 T‐ALL cells led to the demethylation of many genes commonly methylated in T‐ALL. Overall, our results suggest that reduced miR‐29a levels may contribute to the altered epigenetic status of T‐ALL, highlighting its relevance in the physiopathology of this disease. Abstract : Lower levels of miR‐29a were significantly associated with higher blast counts in the BM. Reduced miR‐29a levels may contribute to the altered epigenetic status of T‐ALL. MiR‐29a might contribute to the molecular pathophysiology of T‐ALL.